Incidence, risk factors, and outcomes of osteonecrosis of the jaw: Integrated analysis from three blinded active-controlled phase III trials in cancer patients with bone metastases

F. Saad, J. E. Brown, C. Van Poznak, T. Ibrahim, S. M. Stemmer, Alison T Stopeck, I. J. Diel, S. Takahashi, N. Shore, D. H. Henry, C. H. Barrios, T. Facon, F. Senecal, K. Fizazi, L. Zhou, A. Daniels, P. Carrière, R. Dansey

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Background: Osteonecrosis of the jaw (ONJ) has been reported in patients receiving bisphosphonates for metastatic bone disease. ONJ incidence, risk factors, and outcomes were evaluated in a combined analysis of three phase III trials in patients with metastatic bone disease receiving antiresorptive therapies. Patients and methods: Patients with bone metastases secondary to solid tumors or myeloma were randomly assigned to receive either s.c. denosumab (120 mg) or i.v. zoledronic acid (4 mg) every 4 weeks. On-study oral examinations were conducted by investigators at baseline and every 6 months. Oral adverse events were adjudicated by an independent blinded committee of dental experts. Results: Of 5723 patients enrolled, 89 (1.6%) patients were determined to have ONJ: 37 (1.3%) received zoledronic acid and 52 (1.8%) received denosumab (P = 0.13). Tooth extraction was reported for 61.8% of patients with ONJ. ONJ treatment was conservative in >95% of patients. As of October 2010, ONJ resolved in 36.0% of patients (29.7% for zoledronic acid and 40.4% for denosumab). Conclusions: In this combined analysis of three prospective trials, ONJ was infrequent, management was mostly conservative, and healing occurred in over one-third of the patients. Educating physicians about oral health before and during bone-targeted therapy may help reduce ONJ incidence and improve outcomes.

Original languageEnglish (US)
Pages (from-to)1341-1347
Number of pages7
JournalAnnals of Oncology
Issue number5
Publication statusPublished - May 2012



  • Bone metastases
  • Denosumab
  • Osteonecrosis of the jaw
  • Zoledronic acid

ASJC Scopus subject areas

  • Oncology
  • Hematology

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